Hyaluronic acid (“HA”) is a polysaccharide composed of D-glucuronic acid and N-acetyl-D-glucosamine. It has been used for transdermal drug delivery. HA is found on mammalian cell surfaces, in the basic extra cellular substances of the connective tissues of vertebrates, synovial fluid of joints, vitreous of the eye, tissue of human umbilical cord and in cocks' comb. It is the main component of the extracellular matrix. HA plays an important role in the mechanical support of the cell of many tissues, such as the skin, the tendons, the muscles and cartilage. Since HA binds to its receptor, CD44, on metastatic melanoma cells and hyaluronan is taken up through CD44 and degraded inside the cells, these particles are uniquely suited to specifically detect and destroy these metastatic cells. Like other nanoparticles, HA has several advantages as a carrier of genes, drugs or proteins to these cells. It is less immunogenic or non-immunogenic. Its molecular structure is common in all mammals (HA plays a major component of the extracellular matrix of all tissues). And, derivatives of HA have unique properties for specific biomedical applications without any adverse effects.
HA and its salts are currently being used in various therapies, such as for arthropathies, by intraarticular injection, in opthalmic surgery for intraocular lens implantation, to promote wound healing in various tissues, or, in derivatized and/or crosslinked form, to manufacture thin films or sponges, which are used for tissue separation or other biomedical applications (for review see Band). Strategies have included esterification of HA, acrylation of HA and cross-linking of HA using divinyl sulfone or glycidyl ether. However, these modifications result in decreased solubility in water and/or the chemical reaction strategies used are not designed for cross-linking of HA under physiological conditions (in an aqueous environment, at pH 6.5-8.0). There exists a need in the art for the development of HA nanoparticles. There also exists a need in the art that such particles to be composed of only hyaluronic acid rather than a mixture of two or more polymers.
The invention provides the development of nanoparticles composed of HA, which can be encapsulated and formulated with various peptide, DNA and small molecular drugs for cell specific drug delivery.